Role of a glycocalyx on coronary arteriole permeability to proteins: evidence from enzyme treatments

Abstract

Whereas the glycocalyx of endothelial cells has been shown to influence solute flux from capillary microvessels, little is known about its contribution to the movement of macromolecules across the walls of other microvessels. We evaluated the hypothesis that a glycocalyx contributes resistance to protein flux measured in coronary arterioles. Apparent solute permeability (P(s)) to two proteins of different size and similar charge, alpha-lactalbumin (alpha-lactalb) and porcine serum albumin (PSA), was determined in arterioles isolated from the hearts of 43 female Yucatan miniature swine. P(s) was assessed in arterioles with an "intact" glycocalyx under control conditions and again after suffusion with adenosine (Ado, 10(-5) M, n = 42 arterioles, N = 29 pigs). In a second set of experiments (n = 21 arterioles, N = 21 pigs) arteriolar P(s) was determined before and after perfusion with enzyme (pronase or heparinase), which was used to digest the glycocalyx. P(s) was assessed a third time on those microvessels after exposure to Ado. Consistent with the hypothesis, P(s) for PSA (P(PSA)(s)) and P(s) for alpha-lactalb (P(alpha-lactalb)(s)) increased from basal levels following enzyme treatment. Subsequent suffusion with Ado, a significant metabolite known to alter coronary vascular smooth muscle tone and permeability, resulted in a significant reduction of basal P(alpha-lactalb)(s) in both untreated and enzyme-treated arterioles. Furthermore, in untreated arterioles, P(PSA)(s) was unchanged by Ado suffusion, whereas Ado induced a pronounced reduction in P(PSA)(s) of enzyme-treated vessels. These data demonstrate that in intact coronary arterioles an enzyme-sensitive layer, most likely at the endothelial cell surface, contributes significantly to net barrier resistance to solute flux.

A biliary HCO3−umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes

“…7 A glycocalyx influences the permeation of charged proteins over the endothelial wall. 53,54 The striking effect of desialylation of the glycocalyx by neuraminidase treatment on pH-dependent cholangiocyte toxicity induced by CDC and GCDC, but not TCDC, supports the idea that polar, negatively charged bile salts are prohibited from entering cholangiocytes and from inducing cell death. We assume that this protective effect of the intact glycocalyx is the result of local stabilization of the biliary HCO À 3 umbrella, enabling the deprotonation of bile acids to bile salts in the close vicinity to the membrane.…”

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

“…Hyaluronan also surrounds vascular endothelial cells as an integrated part of the plasma membrane glycoproteins and glycolipids constituting the glycocalyx. The glycocalyx has been shown to reduce the vascular permeability (Qiao et al, 1995;Henry and Duling, 1999;Huxley and Williams, 2000;van Haaren et al, 2003) and contributes significantly to the hydraulic resistance of the capillary wall (Adamson, 1990). The glycocalyx also restricts the access of blood-borne macromolecules and cells to the luminal surface of the endothelial cells, thus reducing the functional diameter of the microvessels (Henry and Duling, 1999).…”

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

“…The central importance of a vascular pathology underlying the hyperglycemia-associated poor prognosis is becoming increasingly evident. Characteristics of hyperglycemia-induced vasculopathy include decreased endothelium-dependent vasodilation, increased capillary permeability for large proteins such as albumin, swelling of endothelial cells, decreased capillary dimensions and diameters, and thickening of the basal lamina (5,13,20,23,33,41).The endothelial cell glycocalyx, a 0.2-to 0.5-m matrix lining the luminal surface of all blood vessels, is a significant factor in microvascular regulation by its action on volume and permeability of capillaries (1,17,18,29,39). Recent evidence demonstrated a role of the glycocalyx in models of ischemiareperfusion injury, inflammation, and altered lipoprotein levels (26, 28, 38).…”